The ultimate task of an antiarrhythmia pacemaker is to prevent sudden cardiac death. In most cases, sudden cardiac death is caused by ventricular fibrillation, although asystole may occasionally be involved. Heretofore, antiarrhythmia pacemakers have responded to the detection of arrhythmias by generating a therapy involving electrical stimulation of the heart to terminate fibrillation or tachycardia and return the heart's rate to a normal sinus rhythm. These therapies include antitachycardia pacing (ATP), cardioversion and fibrillation. Other mechanisms for altering heart rate are known, such as administration of antiarrhythmic drugs and selective stimulation of the autonomic nervous system.
The antiarrhythmia pacemaker of the present invention utilizes a combination of electrophysiological and autonomic nervous system stimulation to treat cardiac arrhythmias. The autonomic nervous system, which includes sympathetic and parasympathetic nervous systems, is made up of neurons which regulate activity of cardiac muscle, smooth muscle and glands. Rather than functioning by activating and stimulating organs, the autonomic nervous system modifies activities already performed by an innervated organ.
The sympathetic nervous system is the thoracolumbar portion of the autonomic nervous system. Sympathetic stimulation does not cause the heart muscle to contract, but instead increases heart rate, contraction force, velocity at which action potentials travel over nerve fibers and electrical sensitivity of myocardial cells. In response to sympathetic nerve impulses, postganglionic sympathetic fibers release norepinephrine which increases heart rate by stimulating the sino-atrial (S-A) node to fire more rapidly and by facilitating atrio-ventricular (A-V) conduction.
The parasympathetic nervous system is the craniosacral portion of the autonomic nervous system. In response to parasympathetic impulses, postganglionic parasympathetic fibers release acetycholine to reduce heart rate. Parasympathetic stimulation reduces heart rate by depressing S-A and A-V node activity.
As used herein, the term arrhythmia refers to any fast abnormal rhythm of the heart that is amenable to treatment by electrical discharges. Arrhythmias include supraventricular tachycardia, atrial fibrillation and atrial flutter, ventricular tachycardia, and ventricular flutter and fibrillation. During a tachycardia the heart beats rapidly, with a ventricular rate higher than 100 beats per minute (bpm) and typically above 150 bpm, and an atrial rate as high as 400 bpm.
Tachycardia is often the result of electrical feedback within the heart. A natural beat leads to feedback of an electrical stimulus which prematurely triggers another beat. Several different pacing modalities have been suggested for tachycardia termination, based upon the underlying principle of interposing a stimulated heartbeat shortly before the next premature triggered beat. This disrupts the stability of the feedback loop to allow the heart to revert to sinus rhythm. Such pacing therapy, however, can cause the tachycardia feedback loop to degenerate so that fibrillation ensues.
Ventricular arrhythmias which arise in association with bradycardia occur less frequently when a heart beats at an increased rate. Therefore, patients who are subject to these arrhythmias are commonly treated with chronotropic drugs, such as sympathomimetric amines and atropine. Unfortunately, the results of chronotropic drug therapy are unpredictable. Drugs may aggravate, rather than prevent, arrhythmias. Furthermore, antiarrhythmia drugs do not prevent sudden cardiac death, possibly because the triggering mechanism for fibrillation may be a factor which is not sensitive to the action of these drugs.
One method for preventing ventricular tachycardia and fibrillation in patients with A-V block or bradycardia involves ventricular pacing at normal or overdrive pacing rates (See, e.g., P. M. Zoll, et al., "Ventricular Fibrillation: Treatment and Prevention by External Electric Currents", New England Journal of Medicine, Vol. 262, page 105 (1960)). E. Sowton modified this method in "The Suppression of Arrhythmias by Artificial Pacemaking", Lancet, Vol. 2, page 1098 (1964), to treat ventricular arrhythmias in patients without A-V block.
D. P. Zipes et al., in "Artificial Atrial and Ventricular Pacing in the Treatment of Arrhythmias", Annals of Internal Medicine, Vol. 70, page 885 (1969), found that increasing a patient's heart rate by atrial, rather than ventricular, pacing may confer hemodynamic and electrophysiological advantages by preserving a normal polarization sequence.
R. A. J. Spurrell et al., in "Pacing Techniques in the Management of Supraventricular Tachycardia", Part 2, Journal of Electrocardiology, Vol. 9, page 89 (1979), shows that overdrive pacing of both the atrium and ventricle in an eccentric activation sequence prevents and terminates junctional tachycardias (tachyarrhythmias which arise at the atrio-ventricular junction, such as re-entry). Both slow and fast ventricular rates trigger this therapy. Similarly, M. Akhtar et al., in "Electrophysical Mechanisms for Modification and Abolition of Atrioventricular Junctional Tachycardia with Simultaneous and Sequential Atrial and Ventricular Pacing", Circulation, Vol. 60, page 1443 (1979), observed that regular simultaneous A-V pacing prevents junctional tachycardias. However, this treatment is not appropriate for long-term junctional tachycardia prevention because of the risk of atrial premature beats or atrial tachycardias triggering improperly high ventricular rates, leading to harmful ventricular arrhythmias.
Continuous high rate atrial pacing may control supraventricular or atrial tachycardias, thereby preventing dangerous ventricular arrhythmias, because atrial pacing at a rate higher than a tachycardia rate may block atrio-ventricular transmission to reduce the ventricular rate. J. W. Lister et al., in "Treatment of Supraventricular Tachycardias by Right Alternating Current Stimulation", American Journal of Cardiology, Vol. 29, page 208 (1972), prevented aggravation of atrial tachycardia into atrial fibrillation in this manner and found that ventricular rate in response to atrial fibrillation was less than the originally occurring atrial tachycardia rate. Unfortunately, continuous high rate atrial pacing is limited to short-term use because fluctuations in autonomic tone may cause intermittently higher A-V conduction rates and transmit the atrial high rate directly to the ventricle, risking dangerous ventricular arrhythmias.
J. F. Lopez et al., in "Reducing the Heart Rate in the Dog by Electrical Stimulation", Circulation Research, Vol. 15, page 414 (1964), slows atrial arrhythmias using atrial paired and coupled stimulation, stimulation by two pulses of short duration in which the first pulse stimulates the atrium and the second pulse occurs at a time when the A-V junction is refractory, thus preventing a ventricular response. Paired and coupled stimulation has also been applied in the ventricle, with inconsistent results, to control heart rate in supraventricular arrhythmia, atrial fibrillation and persistent ventricular tachycardia patients.
These techniques effectively prevent tachycardias for short periods of time under the direct supervision of a health care professional. However, the risk of initiating or aggravating dangerous arrhythmias due to the inability to adapt to varied physiological circumstances renders these methods and devices inappropriately dangerous for long-term, automatic use. What is needed is a technique for long-term arrhythmia prevention in an automatic, implantable system.
J. I. Haft et al., in "Electrical Conversion of Atrial Flutter without Ventricular Depolarization", Circulation, Vol. 34: III, page 118 (1966), terminated atrial tachycardia and atrial flutter using rapid repetitive atrial stimulation. Results of this therapy were inconsistent, with a high incidence of atrial fibrillation, but were improved considerably by augmenting pacing with the application of antiarrhythmic agents.
G. Neumann et al., in "A Study of Electrophysiological Changes During Rapid Atrial Burst Stimulation Associated with Reentry Tachycardias", Presentations of the 1st European Symposium of Cardiac Pacing, London, page 23 (1978), improved upon the technique of rapid repetitive stimulation by devising a pacemaker in which the initial interval between an atrial event and delivery of a burst was required to exceed 250 ms, thus avoiding early stimulation in the vulnerable phase with its risk of initiating atrial fibrillation. Another solution to this problem is termed "autodecremental" pacing in which the initial coupling interval of a burst is delivered very late in the tachycardia cycle but is followed by a gradual acceleration of the pacing rate up to a limit determined by the pacing interval. (See, e.g., A. J. Camm et al., "A Microcomputer-Based Tachycardia Termination System--A Preliminary Report", in Journal Medical Engineering Technical, Vol. 4, page 80 (1980)). Long-term results using rapid repetitive stimulation techniques are disappointing due to provocation of atrial fibrillation.
Underdrive pacing, using critically coupled premature beats, is an alternative to rapid repetitive stimulation for the termination of arrhythmias. N. C. Hunt et al., in "Conversion of Supraventricular Tachycardias with Atrial Stimulation--Evidence for Reentry Mechanism", Circulation, Vol. 38, page 1060 (1968), used underdrive pacing in which, sooner or later by random competition, an appropriately times stimulus occurs and terminates a tachycardia. Unfortunately, underdrive pacing is usually ineffective if a tachycardia rate exceeds 160 beats per minute. Since antitachycardia therapy is commonly not activated until tachycardia rate is above about 140 beats per minute, there is only a narrow range of tachycardia rates and a small proportion of tachycardias which automatic underdrive pacing may assist.
Most recently, pacing by critically timed premature beat pulses has been employed to terminate tachycardias. A pacemaker scans the heart's diastolic period of the tachycardia cycle with one or more stimuli to provide critical timing.
All of these cardiac arrhythmias treatment techniques involve delivery of stimulation pulses to cardiac tissue. Cardiovascular system performance is also affected by techniques which alter autonomic nervous system function. Modified autonomic nervous system activity, by sectioning or cold blocking of nerve impulses or by autonomic nerve stimulation, has been employed to alter heart rate. For example, P. J. Schwartz et al. in "Sympathetic Imbalance and Cardiac Arrhythmias", from Nervous Control of Vascular Function, Randall WC ed., Oxford University Press (1984), expresses that electrical stimulation of sympathetic nerves lowers the ventricular fibrillation threshold and increases vulnerability to fibrillation. In contrast, electrical stimulation of parasympathetic nerves raises the ventricular fibrillation threshold by depressing action of sympathetic nerves. Note that if sympathetic activity is low already, no change can be expected by deactivating sympathetic nerves.
M. Stramba-Badiale et al. found that parasympathetic nervous system stimulation by vagus nerve excitation is advantageous for treating arrhythmias, in "Sympathetic-Parasympathetic Interaction and Accentuated Antagonism in Conscious Dogs", American Journal of Physiology, Vol. 260 (2Pt 2): pages H335-340 (Feb 91). Vagal activity contributes to cardiac electrical stability. Conversely, a decreased vagal tone and reflex is associated with a heightened risk of sudden cardiac death.
G. Zuanetti et al. in "Protective Effect of Vagal Stimulation on Reperfusion Arrhythmias in Cats", Circulation Research Vol. 61(3), pages 429-435 (1987) found that combined bradycardia pacing and vagal stimulation protected against sustained ventricular tachycardia, whereas pacing alone aggravated or initiated arrhythmias. Zuanetti did not attempt nerve stimulation in combination with arrhythmia therapy, such as antitachycardia pacing, cardioversion or defibrillation.
These prior art systems either, in the first instance, employ antiarrhythmia pacing, cardioversion or defibrillation in response to the detection of a rapid cardiac rhythm to terminate such an arrhythmia; or, alternatively, utilize constant long-term autonomic nervous system modification to prevent arrhythmias. The prior art does not appear to disclose an apparatus or method for detecting a cardiac abnormality, including precursors to arrhythmias, tachyarrhythmias or fibrillation and, in response to such detection, applying a combined therapy of antiarrhythmia pacing and autonomic nerve stimulation.